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Boosting compromised SARS-CoV-2-specific immunity with mRNA vaccination in liver transplant recipients

BACKGROUND & AIMS: Liver transplant recipients (LTRs) demonstrate a reduced response to COVID-19 mRNA vaccination; however, a detailed understanding of the interplay between humoral and cellular immunity, especially after a third (and fourth) vaccine dose, is lacking. METHODS: We longitudinally...

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Autores principales: Luxenburger, Hendrik, Reeg, David B., Lang-Meli, Julia, Reinscheid, Matthias, Eisner, Miriam, Bettinger, Dominik, Oberhardt, Valerie, Salimi Alizei, Elahe, Wild, Katharina, Graeser, Anne, Karl, Vivien, Sagar, Emmerich, Florian, Klein, Florian, Panning, Marcus, Huzly, Daniela, Bengsch, Bertram, Boettler, Tobias, Elling, Roland, Thimme, Robert, Hofmann, Maike, Neumann-Haefelin, Christoph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019593/
https://www.ncbi.nlm.nih.gov/pubmed/36804404
http://dx.doi.org/10.1016/j.jhep.2023.02.007
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author Luxenburger, Hendrik
Reeg, David B.
Lang-Meli, Julia
Reinscheid, Matthias
Eisner, Miriam
Bettinger, Dominik
Oberhardt, Valerie
Salimi Alizei, Elahe
Wild, Katharina
Graeser, Anne
Karl, Vivien
Sagar
Emmerich, Florian
Klein, Florian
Panning, Marcus
Huzly, Daniela
Bengsch, Bertram
Boettler, Tobias
Elling, Roland
Thimme, Robert
Hofmann, Maike
Neumann-Haefelin, Christoph
author_facet Luxenburger, Hendrik
Reeg, David B.
Lang-Meli, Julia
Reinscheid, Matthias
Eisner, Miriam
Bettinger, Dominik
Oberhardt, Valerie
Salimi Alizei, Elahe
Wild, Katharina
Graeser, Anne
Karl, Vivien
Sagar
Emmerich, Florian
Klein, Florian
Panning, Marcus
Huzly, Daniela
Bengsch, Bertram
Boettler, Tobias
Elling, Roland
Thimme, Robert
Hofmann, Maike
Neumann-Haefelin, Christoph
author_sort Luxenburger, Hendrik
collection PubMed
description BACKGROUND & AIMS: Liver transplant recipients (LTRs) demonstrate a reduced response to COVID-19 mRNA vaccination; however, a detailed understanding of the interplay between humoral and cellular immunity, especially after a third (and fourth) vaccine dose, is lacking. METHODS: We longitudinally compared the humoral, as well as CD4+ and CD8+ T-cell, responses between LTRs (n = 24) and healthy controls (n = 19) after three (LTRs: n = 9 to 16; healthy controls: n = 9 to 14 per experiment) to four (LTRs: n = 4; healthy controls: n = 4) vaccine doses, including in-depth phenotypical and functional characterization. RESULTS: Compared to healthy controls, development of high antibody titers required a third vaccine dose in most LTRs, while spike-specific CD8+ T cells with robust recall capacity plateaued after the second vaccine dose, albeit with a reduced frequency and epitope repertoire compared to healthy controls. This overall attenuated vaccine response was linked to a reduced frequency of spike-reactive follicular T helper cells in LTRs. CONCLUSION: Three doses of a COVID-19 mRNA vaccine induce an overall robust humoral and cellular memory response in most LTRs. Decisions regarding additional booster doses may thus be based on individual vaccine responses as well as evolution of novel variants of concern. IMPACT AND IMPLICATIONS: Due to immunosuppressive medication, liver transplant recipients (LTR) display reduced antibody titers upon COVID-19 mRNA vaccination, but the impact on long-term immune memory is not clear. Herein, we demonstrate that after three vaccine doses, the majority of LTRs not only exhibit substantial antibody titers, but also a robust memory T-cell response. Additional booster vaccine doses may be of special benefit for a small subset of LTRs with inferior vaccine response and may provide superior protection against evolving novel viral variants. These findings will help physicians to guide LTRs regarding the benefit of booster vaccinations.
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spelling pubmed-100195932023-03-17 Boosting compromised SARS-CoV-2-specific immunity with mRNA vaccination in liver transplant recipients Luxenburger, Hendrik Reeg, David B. Lang-Meli, Julia Reinscheid, Matthias Eisner, Miriam Bettinger, Dominik Oberhardt, Valerie Salimi Alizei, Elahe Wild, Katharina Graeser, Anne Karl, Vivien Sagar Emmerich, Florian Klein, Florian Panning, Marcus Huzly, Daniela Bengsch, Bertram Boettler, Tobias Elling, Roland Thimme, Robert Hofmann, Maike Neumann-Haefelin, Christoph J Hepatol Research Article BACKGROUND & AIMS: Liver transplant recipients (LTRs) demonstrate a reduced response to COVID-19 mRNA vaccination; however, a detailed understanding of the interplay between humoral and cellular immunity, especially after a third (and fourth) vaccine dose, is lacking. METHODS: We longitudinally compared the humoral, as well as CD4+ and CD8+ T-cell, responses between LTRs (n = 24) and healthy controls (n = 19) after three (LTRs: n = 9 to 16; healthy controls: n = 9 to 14 per experiment) to four (LTRs: n = 4; healthy controls: n = 4) vaccine doses, including in-depth phenotypical and functional characterization. RESULTS: Compared to healthy controls, development of high antibody titers required a third vaccine dose in most LTRs, while spike-specific CD8+ T cells with robust recall capacity plateaued after the second vaccine dose, albeit with a reduced frequency and epitope repertoire compared to healthy controls. This overall attenuated vaccine response was linked to a reduced frequency of spike-reactive follicular T helper cells in LTRs. CONCLUSION: Three doses of a COVID-19 mRNA vaccine induce an overall robust humoral and cellular memory response in most LTRs. Decisions regarding additional booster doses may thus be based on individual vaccine responses as well as evolution of novel variants of concern. IMPACT AND IMPLICATIONS: Due to immunosuppressive medication, liver transplant recipients (LTR) display reduced antibody titers upon COVID-19 mRNA vaccination, but the impact on long-term immune memory is not clear. Herein, we demonstrate that after three vaccine doses, the majority of LTRs not only exhibit substantial antibody titers, but also a robust memory T-cell response. Additional booster vaccine doses may be of special benefit for a small subset of LTRs with inferior vaccine response and may provide superior protection against evolving novel viral variants. These findings will help physicians to guide LTRs regarding the benefit of booster vaccinations. The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. 2023-05 2023-02-18 /pmc/articles/PMC10019593/ /pubmed/36804404 http://dx.doi.org/10.1016/j.jhep.2023.02.007 Text en © 2023 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Research Article
Luxenburger, Hendrik
Reeg, David B.
Lang-Meli, Julia
Reinscheid, Matthias
Eisner, Miriam
Bettinger, Dominik
Oberhardt, Valerie
Salimi Alizei, Elahe
Wild, Katharina
Graeser, Anne
Karl, Vivien
Sagar
Emmerich, Florian
Klein, Florian
Panning, Marcus
Huzly, Daniela
Bengsch, Bertram
Boettler, Tobias
Elling, Roland
Thimme, Robert
Hofmann, Maike
Neumann-Haefelin, Christoph
Boosting compromised SARS-CoV-2-specific immunity with mRNA vaccination in liver transplant recipients
title Boosting compromised SARS-CoV-2-specific immunity with mRNA vaccination in liver transplant recipients
title_full Boosting compromised SARS-CoV-2-specific immunity with mRNA vaccination in liver transplant recipients
title_fullStr Boosting compromised SARS-CoV-2-specific immunity with mRNA vaccination in liver transplant recipients
title_full_unstemmed Boosting compromised SARS-CoV-2-specific immunity with mRNA vaccination in liver transplant recipients
title_short Boosting compromised SARS-CoV-2-specific immunity with mRNA vaccination in liver transplant recipients
title_sort boosting compromised sars-cov-2-specific immunity with mrna vaccination in liver transplant recipients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019593/
https://www.ncbi.nlm.nih.gov/pubmed/36804404
http://dx.doi.org/10.1016/j.jhep.2023.02.007
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